Dopamine D4 receptors: a new opportunity for research on schizophrenia.
Classically, the D2 receptors formed the core of the dopamine hypothesis for schizophrenia. Recently, the dopamine D4 receptors have received particular attention in this context. This is due to the atypical antipsychotic, clozapine, which is effective in treating refractory schizophrenics without the side-effect profile of typical neuroleptics, and displays a ten-fold higher affinity for D4 compared to D2 or D3 receptors. Following various reports presenting the interest of D4 receptors in treating schizophrenia, multiple chemical developments were made. During the last five years, various structures were described with a high selectivity for D4 receptor subtype. Currently, although the first clinical report was very disappointing, the observation which support the idea that D4 might serve as a target for clozapine have significantly modified and extended the understanding of mechanism underlying atypical antipsychotic treatment of schizophrenia.
Liégeois
J
J
Laboratory of Medicinal Chemistry, University of Liège, rue Fusch 3, Liège, B-4000, Belgium. jf.Liegeois@ulg.ac.be
Eyrolles
L
L
Bruhwyler
J
J
Delarge
J
J
D014150:Antipsychotic Agents / Q000737:chemistry / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D003024:Clozapine